Journal
CELLULAR SIGNALLING
Volume 24, Issue 3, Pages 770-778Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2011.11.012
Keywords
Ion channel; ATP; Stem cell; Receptor; Survival; P2X receptor
Categories
Funding
- Wellcome Trust [084562/Z/07/Z, 08780/Z/08/Z]
- University of Bath
- Medical Research Council [G0801108]
- MRC [G0801108] Funding Source: UKRI
- Medical Research Council [G0801108] Funding Source: researchfish
- Wellcome Trust [084562/Z/07/Z] Funding Source: Wellcome Trust
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The growth of a pluripotent embryonic stem (ES) cell population is dependent on cell survival, proliferation and self-renewal. The nucleotide ATP represents an important extracellular signalling molecule that regulates the survival of differentiated cells, however, its role is largely undefined in embryonic stem cells. Here we report a role for ATP-gated P2X7 receptors in ES cell survival. The functional expression of P2X7 receptors in undifferentiated mouse ES cells is demonstrated using a selective P2X7 antagonist and small interfering RNA knockdown of these receptors. Our data illustrate a key role for the P2X7 receptor as an essential pro-survival signal required for optimal ES cell colony growth in the presence of leukemia inhibitor factor (LIF). However, chronic exposure to exogenous ATP leads to rapid P2X7-dependent cell death via necrosis. Together, these data demonstrate a novel role for P2X7 receptors in regulation of ES cell behaviour where they can mediate either a pro-survival or pro-death signal depending on the mode of activation. (C) 2011 Elsevier Inc. All rights reserved.
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